This proposal addresses three interrelated aspects of the effects of pregnancy on the immune response in humans. Firstly, the transplacental passage of antigen will be studied. Mutual sensitization to the same antigen between mother and offspring will be examined in order to detect active immunization of the offspring. Mothers will be immunized with tetanus toxoid during pregnancy to induce active, protective immunization in her offspring. In the course of this study, evidence will be obtained for the presence of serum factors in the mother and the neonate which can depress, or possibly stimulate, the immune response. If such factors can be clearly defined, we will proceed to isolate and characterize them. These studies will help to define the immunological status in pregnancy and lead to the development of methods for "immunological engineering" whereby the immunization of the mother can endow her child with protection against a variety of infectious diseases and possibly also against oncogenic viruses. Secondly, the role of antibody in influencing organogenesis will be investigated using the disaggregation and induction systems. The transplacental passage of maternal antibodies, and possibly antibody production by the fetus, could lead to organ malformation or death of the fetus. Thirdly, the transplacental passage of cells during gestation and at delivery will be studied. This process can stimulate the immune system of the fetus, especially in the presence of maternal disease such as toxemia and diabetes or with late clamping of the cord at delivery. This sensitization could lead to a variety of immunologically mediated diseases in the newborn, including AB or Rh hemolytic disease. This study will also lead to the development of sensitive immunological techniques that will have immediate applicability to monitoring pregnancies where there is a possibility of Rh disease. In summary, this research program will provide basic information regarding the immunological aspects of gestation in humans; it will afford insight into some immunologically mediated diseases initiated in the offspring during pregnancy; and it will lead to several practical techniques for the prevention and diagnosis of disease in the fetus and in the newborn.